Moss-associated metabolites decrease antibiotic-resistant Enterobacterales in urban environment

Human activity intensifies the spread of antibiotic resistance genes (ARGs), threatening environmental and public health. Plant metabolite-microbe interactions play a crucial role in mitigating ARGs by shaping the soil environment. However, the role of mosses and their metabolites in mitigating ARG risks in natural settings remains largely unexplored. In this study, we conducted paired surveys of moss-covered and bare soils across urban and suburban parks, and found that moss cover significantly reduced ARG abundance. This mitigation effect was most pronounced in urban parks, where human-induced changes led to significant enrichment of Enterobacterales, the primary microbial host within ARG profiles strongly correlated with ARG levels. Moss presence led to the suppression of these high-risk hosts through the selective accumulation of the moss secondary metabolite, cristacarpin, in the underlying soil. Microcosm experiments further confirmed that cristacarpin reduced both Enterobacterales and ARGs, while molecular simulations suggested that this effect may be associated with cristacarpin binding to MlaC, a protein involved in outer membrane lipid transport and integrity. Comparison of published data from 2938 soil samples across the globe confirmed that Enterobacterales were consistently enriched in areas under higher anthropogenic pressure, highlighting the potential of mosses to mitigate the spread of ARGs in human-impacted areas worldwide. Our findings support the consideration of mosses as a scalable, nature-based, contribution to limiting the spread of ARGs, offering novel opportunities to mitigate antimicrobial resistance risks in anthropogenically-disturbed environments worldwide.